Acute respiratory infection emergency access in a tertiary care children hospital in Italy, prior and after the SARS‐CoV‐2 emergence

Abstract Background The COVID‐19 pandemic has changed the epidemiology of acute respiratory infections (ARIs) in children. The aims of the present study were to describe the epidemiological trend of ARI emergency visits and virology results prior and after the SARS‐CoV‐2 emergence and to estimate the association of ARI emergency department (ED) visits with respiratory viruses. Methods This study was conducted at the Bambino Gesù Children's Hospital, a tertiary care children's hospital in the Lazio Region, Italy. The demographic and clinical information of children who accessed the ED and were diagnosed with ARI from January 1, 2018 to June 30, 2022 was retrospectively extracted from the electronic health records. The observed temporal trends in viruses diagnosed from respiratory samples were compared with the number of ARI ED visits over the same period through a multivariable linear regression model. Results During the study period, there were 72,959 ED admissions for ARIs and 33,355 respiratory samples resulted positive for viruses. Prior to the pandemic, respiratory syncytial virus (RSV) and influenza had a clear seasonal pattern, which was interrupted in 2020. In 2021–2022, RSV reached the highest peak observed during the study period, whereas influenza activity was minimal. The peaks of ARI ED visits corresponded to peaks of influenza, RSV, and rhinovirus in the 2018–2019 and 2019–2020 seasons, to SARS‐CoV‐2 and rhinovirus in 2020, and to RSV and parainfluenza in 2021–2022. Conclusions ARI resulting in ED visits should be included in the ARI disease burden measurement for a more accurate measure of the impact of preventive measures.


| INTRODUCTION
Acute respiratory infections (ARIs) are the most common cause of pediatric emergency visits 1 and are most frequently caused by viruses, such as rhinovirus, enterovirus, respiratory syncytial virus (RSV), influenza virus, parainfluenza virus, bocaviruses, adenoviruses, and metapneumovirus. [2][3][4][5] Italy was the first country to be affected by COVID-19 in Europe, with the first native patient diagnosed on February 20, 2020. National response actions to contain the pandemic upgraded from strict social distancing measures in 11 municipalities in Northern Italy, on February 23, 2020, to national social distancing and school closures on March 4, 2020 and culminated with the national lockdown from March 11 to May 4, 2020. 6 From October 2020 to June 2021, social distancing measures were progressively reduced and adapted according to the evolution of the COVID-19 pandemic.
The COVID-19 pandemic has deeply changed the epidemiology of ARIs in children; public health measures introduced to prevent the pandemic affected the transmission of respiratory viruses, 7,8 interfered with the seasonality of childhood respiratory diseases and reduced ED visits and hospitalizations due to ARIs. 7,9,10 With the reduction of social isolation measures, an unexpected RSV seasonality was observed in 2021-2022, with an earlier peak of shorter duration in comparison with pre-pandemic seasons. 11,12 Regression models are frequently used to determine what proportion of the outcome of interest (such as outpatient visits, ED visits or hospitalizations) might be attributable to specific infections, such as influenza. [13][14][15] The aims of the present study were to describe the epidemiological trend of ARI emergency visits and virology results in a tertiary care children hospital and to estimate the association of ARI ED visits with respiratory viruses, from January 2018 to June 2022.

| Data collection
The demographic and clinical information of children who accessed the ED and were diagnosed with ARI from January 1, 2018 to June 30, 2022 was retrospectively extracted from the electronic health records of OPBG.
In detail, information on ED visits was collected from the OPBG Healthcare Emergency Information System (HEIS), which includes patient demographics, ICD-9-CM diagnosis, and status at discharge (i.e., hospitalized or discharged at home). ARI was defined according to the ICD-9 CM diagnosis at discharge (see supporting information S1).
Information on virology results of respiratory samples (i.e., nasopharyngeal swabs, tracheal swabs, and/or broncho-alveolar lavages) obtained in the same time period from OPBG patients was derived from the Hospital Electronic Laboratory Information System. Respiratory samples testing positive for the same virus within 3 months were excluded from the analysis.  Starting from 2020, SARS-CoV-2 molecular assay or SARS-CoV-2 antigen tests were also performed.

| Statistical analysis
The number of ED admissions and positive tests by year, week, and age class were summarized as counts and percentages; positive tests were also described by type of virus; significance in trend was tested using Cochrane Armitage test.
The observed temporal trends in viruses diagnosed from respiratory samples were compared with the number of ARI ED visits over the same time period. The latter was used as the dependent variable of a multiple linear regression. The independent variables were the weekly number of viral laboratory results. The expected number of ARI ED visits Yj in a week period j was the following: where Lij is the number of laboratory reports for virus i in week j, αi is

| RESULTS
From January 2018 to June 2022, there were 72,959 ED visits for ARIs (Table 1). In 2020, the number of ARI ED visits decreased by    The best goodness-of-fit of the models by age group was in infants  wearing and social distancing on preventing transmission of influenza and the reduction of national and travels that facilitate its spreading. 23 We confirmed that RSV is the leading cause of ARI in young children and has a high seasonality, 8 which was disrupted by the COVID-19 pandemic. After the reduction of cases in 2020, the peak of RSV incidence in 2021-2022 was striking. As reported by other authors, this may be due to the increasing number of children that were naive for RSV, due to the lack of RSV circulation in the population during the strict social distancing measures for the SARS-CoV-2 pandemic. 8 We documented a similar picture for parainfluenza, which in 2021-2022 reached the highest peak observed since 2018. A resurgence of parainfluenza was observed also in China, in a nationwide study that reported its increase in the <18-year-old group, when schools were re-opened in most provinces in 2020-2021. 24 In this study, the regression model estimates of ARI visits corresponded closely with the observed weekly numbers in children <5 years of age, where ARIs are a leading cause of morbidity and mortality. 25 We documented that almost 60% of the ARIs in all the age groups of children can be attributed to a viral infection and that different viruses play a role in different age groups. RSV was common in infants under the age of 1 year, whereas influenza was responsible for most ED admissions in children aged 6-9 years. Our results were also consistent with a recent modeling study reporting that individuals F I G U R E 3 Multivariable linear regression models -weekly emergency department (ED) acute respiratory infection (ARI) visits by age group; Ospedale Pediatrico Bambino Gesù (OPBG), January 2018 to June 2022 by age group.
aged 5-14 years were the most affected by influenza virus compared with other age groups. 26 This finding is of particular interest because from the 2020/2021 season, the Ministry of Health has recommended influenza vaccination in healthy children aged between 6 months and 6 years, in Italy. 27 The recommendation was based on the high incidence of cases of influenza-like illness (ILI) (not laboratory confirmed, though) reported to the national influenza surveillance system (InfluNet) in the 0-5 age group. 28

AUTHOR CONTRIBUTIONS
MCDA and CR conceived the study; MCDA, CR, and CD wrote the manuscript; LR performed statistical analysis; AR, MAB, PB, CR, AV, CFP, and MR reviewed the manuscript. All the authors reviewed the final version of the manuscript and agreed to be accountable for the content of the work.

CONFLICT OF INTEREST
The authors declare that they have no competing interests.

DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.

ETHICS APPROVAL STATEMENT
The study was approved by the Ethics Committee of the Bambino Gesù Children's Hospital.

PEER REVIEW
The peer review history for this article is available at https://publons. com/publon/10.1111/irv.13102.

PATIENT CONSENT STATEMENT
Considering the retrospective study design, written informed consent was not deemed necessary.

SOURCES
Not applicable.